Low Circulating Vitamin B6 And Inflammation Of Marker C-Reactive Protein - Brief Article

Nutrition Research Newsletter, July, 2001

Lower vitamin B6 concentrations are reported to confer an increased and independent risk for cardiovascular disease (CVD). The mechanism underlying this relationship, however, remains to be defined. Other diseases, such as rheumatoid arthritis, are associated with reduced vitamin B6 levels. Despite a clear distinction in pathophysiology, inflammatory reaction may be the major link between these diseases. The researchers of this recently published study hypothesized a relationship between pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, and the marker of inflammation C-reactive protein (CRP). They evaluated whether total plasma homocysteine (tHcy), a well-defined risk factor for CVD and a major determinant of plasma PLP levels, had a possible role as a mediator of this hypothesized relationship.

Data from 891 participants from the population-based Framingham Heart Study cohort were analyzed. (The Framingham Heart Study cohort is an epidemiological study established in Framingham, MA, from 1948 through 1950.) The original cohort consisted of 5209 subjects of both sexes 30 to 62 years old. The surviving members of this cohort have been examined every 2 years, and in 1988 and 1989, 1402 survivors participated in the 20th examination. Samples of venous blood were drawn from each subject to determine the concentration of CRP, tHcy, folate, vitamin B12, and PLP. Subjects were divided into two groups according to normal or elevated CRP values. Plasma PLP levels were substantially lower in group 2 than in group 1 (mean values in group 2, 36.5 nmol/L versus 55.8 nmol/L in group 1, P [is less than] 0.001). In a multiple logistic regression model adjusted for tHcy, the association of PLP with CRP remained highly significant (P=0.003).

These data demonstrate a strong association between decreased plasma PLP and increased levels of CRP, a major systemic marker of inflammation. Moreover, the association of PLP with CRP remained highly significant even after adjustment for tHcy, which is known to be an important metabolic indicator of vitamin B6 status as well as a cardiovascular risk factor. Furthermore, the low vitamin B6 levels were not attributable to impaired dietary intake, because it was similar in the two groups.

Low plasma PLP is associated with higher CRP levels independently of tHcy. This observation may reflect a vitamin B6 utilization in the presence of an underlying inflammatory process and represent a possible mechanism to explain the decreased vitamin B6 levels in CVD. The present study confirms observations from others of a lack of association of increased CRP and tHcy levels, suggesting that the relationship between tHcy and atherosclerosis cannot be explained through a link with CRP per se, whereas both are independent risk factors for CVD.

Various conditions such as renal failure, smoking, and age are known to be associated with reduced levels of PLP. In addition, PLP. the predominant form of plasma vitamin B6, is primarily bound to albumin, whose diminished levels may result in lower values of circulating PLP. Adjustment for albumin, creatinine, age, sex, and smoking, however, did not affect the observed association. Additional studies are necessary to clarify whether inflammation-associated decreases in circulating PLP play a role in the cascade of metabolic events related to certain diseases.

S. Friso, P. Jacques, P. Wilson, I. Rosenberg, J. Selhub. Low Circulating Vitamin B6 Is Associated With Elevation of the Inflammation Marker C-Reactive Protein Independently of Plasma Homocysteine Levels. Clinical Investigation and Reports (June 2001) [Correspondence: Jacob Selhub, PhD, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, 711 Washington St, Boston, MA 02111. E-mail: jselhub@hnrc.tufts.edu].